First-line Ibrutinib Plus Venetoclax Showed Significant, Durable Response for Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Overall, the investigators observed that the CR, undetectable minimal residual disease rates, progression free survival, and overall survival amomg the patients enrolled in the trial were favorable.

First-line ibrutinib plus venetoclax was seen to provide deep, durable responses in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), including in those with genomic high-risk features, according to a poster presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

The CAPTIVATE study assessing first-line treatment with ibrutinib plus venetoclax for CLL is a multicenter phase 2 study that analyzed data from patients aged 70 years or younger who had previously untreated CLL/SLL and had received 3 cycles of ibrutinib plus venetoclax and then 12 cycles of ibrutinib plus venetoclax (ibrutinib at 420 mg/d orally; venetoclax ramp-up to 400 mg/d orally).

Among the 159 patients enrolled in the study, high-risk features observed in the patient population included del(17p)/TP53 mutation (17%), del(11q) (18%), complex karyotype (19%), and unmutated IGHV (56%). In total, 147 (92%) patients completed planned first line treatment with ibrutinib and and 149 (94%) patients completed planned first line treatment with venetoclax, respectively.

The median time patients spent enrolled in the study was 27.9 month (range, 0.8–33.2), while the complete response (CR) rate was 55% (95% CI 48–63) for patients who were treated with fixed-duration ibrutinib plus venetoclax in the overall population, which was consistent across high-risk subgroups. Further, out of the 88 patients who achieved CR, 78 had durable CR. However, 1 patient died 7 months after CR and the other 9 patients were not evaluable.

In the trial, the adverse events (AEs) were primarily classified as grade 1 or 2, and grade 3 or 4 AEs were neutropenia (33%), hypertension (6%), and neutrophil count decreased (5%). The safety profile of ibrutinib plus venetoclax was consistent with known AEs for each agent, and no new safety signals were identified. Overall, the investigators observed that the CR, undetectable minimal residual disease rates, progression free survival, and overall survival amomg the patients enrolled in the trial were favorable.

With these results, the researchers were able to ascertain that first-line ibrutinib plus venetoclax can provide deep, durable responses in patients with CLL/SLL, including for patients with genomic high-risk features, while remaining a fixed-duration regimen that is oral only, once-daily, and chemotherapy-free.

REFERENCE

Fixed-duration (FD) first-line treatment (tx) with ibrutinib (I) plus venetoclax (V) for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Primary analysis of the FD cohort of the phase 2 captivate study. 2022 ASCO Annual Meeting. Accessed June 7, 2022. https://meetings.asco.org/abstracts-presentations/201560